Study Discovers Cells That Put Hair Follicles to Sleep

In male and female pattern baldness, many hair follicles still exist but are dormant. The search for new drugs that reawaken follicles and induce hair growth has been limited by the field’s focus on finding drugs that work along the same pathways as finasteride and minoxidil, the only two drugs currently available for men with male pattern baldness.

Christiano and her colleagues previously discovered a new pathway, called JAK-STAT, that is active inside the stem cells of resting hair follicles and keeps them in a dormant state. They previously demonstrated that JAK inhibitors applied to mouse skin are a potent way to reawaken resting hair follicles in mice.

In their latest study, the researchers wanted to get a detailed picture of the natural processes that keep follicles dormant, so they looked for factors that controlled the JAK pathway activity in the hair follicle.

By Columbia University Irving Medical Center. On June 25, 2019. https://www.cuimc.columbia.edu/news/studies-uncover-new-approaches-combat-hair-loss-men-and-women

New Cells Called Trichophages

The search revealed a previously unknown immune-related cell type that produces a substance known as Oncostatin M that keeps the follicles in a state of dormancy. “Rare subsets of immune cells were previously difficult to identify in whole skin, but this work was facilitated by our ability to sequence individual cells and pinpoint the ones making Oncostatin M,” says Etienne Wang, PhD, first author of the study. These cells are most similar to macrophages, which are scavenger cells of the immune system, and the team found them in close association with resting hair follicles.

The researchers named these cells trichophages, after the Greek word tricho for hair.

Targeting the trichophages can also turn on the hair cycle. By using small molecule inhibitors and antibodies to block Csf1R, a receptor on the trichophages, the researchers could block the flow of Oncostatin M and restart the hair cycle.

Reawakening Dormant Hair Follicles with New Drugs

“Our previous studies implicated JAK-STAT signaling as one potential new therapeutic pathway for hair loss disorders by targeting hair follicle stem cells with JAK inhibitors,” Christiano says. (A biotech company recently reported(link is external and opens in a new window) results of a small phase 2 trial of a topical JAK-STAT inhibitor based on these studies.) “Here, we show that blocking the source of the JAK activating signal outside the hair follicle is another way to target this mechanism.”

Most drug development has focused on treatments for male pattern hair loss, and the majority of clinical trials are conducted exclusively in men.

“These new pathways may lead to new treatments for both men and women suffering from hair loss, since they appear to be acting independently of male hormone pathways,” Christiano says. “Especially if treatments are used topically, that could avoid the related side effects seen with finasteride and minoxidil.”

Growing New Hair Follicles in a Dish

In a second study, aimed at using stem cells for hair growth, the Columbia researchers have created a way to grow human hair in a dish, which could open up hair restoration surgery to more people, including women, and improve the way pharmaceutical companies search for new hair growth drugs.

It is the first time that human hair follicles have been entirely generated in a dish, without the need for implantation into skin.

For years it’s been possible to grow mouse or rat hairs in the lab by culturing cells taken from the base of existing follicles.

“Cells from rats and mice grow beautiful hairs,” Christiano says. “But for reasons we don’t totally understand, human cells are resistant.”

To break the resistance of human hair cells, Christiano has been trying to create conditions that mimic the 3D environment human hair cells normally inhabit. The lab first tried creating little spheres of cells inside hanging drops of liquid. But when the spheres were implanted in mice, the results were unpredictable: The cells from some people created new hair while others didn’t.